The Hippo Signaling Pathway, Reactive Oxygen Species Production, and Oxidative Stress: A Two-Way Traffic Regulation

The Hippo signaling pathway is recognized for its significant role in cell differentiation, proliferation, survival, and tissue regeneration. Recently, the Hippo signaling pathway was also found to be associated with oxidative stress and reactive oxygen species (ROS) regulation, which are important in the regulation of cell survival. Studies indicate a correlation between components of the Hippo signaling pathway, including MST1, YAP, and TAZ, and the generation of ROS. On the other hand, ROS and oxidative stress can activate key components of the Hippo signaling pathway. For example, ROS production activates MST1, which subsequently phosphorylates FOXO3, leading to apoptotic cell death. ROS was also found to regulate YAP, in addition to MST1/2. Oxidative stress and ROS formation can impair lipids, proteins, and DNA, leading to many disorders, including aging, neurodegeneration, atherosclerosis, and diabetes. Consequently, understanding the interplay between the Hippo signaling pathway, ROS, and oxidative stress is crucial for developing future disease management strategies. This paper aimed to review the association between the Hippo signaling pathway, regulation of ROS production, and oxidative stress to provide beneficial information in understanding cell function and pathological processes.